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Abstract Background Epidermolysis bullosa (EB) is an inherited genodermatosis of variable severity characterised by skin and mucosal fragility commonly associated with altered gait patterns and hypermobility. Objectives To define the altered gait pattern and identify possible causes in patients with EB. Methods Retrospective review of the EB database to identify children with EB with at least one physiotherapy assessment between 2009 and 2022. Results Forty‐eight children out of 59 referrals to physiotherapy with an altered gait pattern were identified (81.3%); 23 (48%) had recessive dystrophic EB (RDEB), 17 (36%) EB simplex, five (10%) Junctional EB (JEB) and three (6%) dominant dystrophic EB (DDEB). The patho‐mechanical altered gait patterns were characterised by altered load‐bearing surface in contact with the floor (63%), short shuffling pattern with high cadence and decreased single support (42%) and equinovarus (toe walking) (6%). Hypermobility (as defined by the Beighton score) was present in 67% of patients: 43% in RDEB, 88% in EBS, 100% in JEB and 67% in DDEB. Conclusions In this study, we provide the first accurate data for the causes of altered gait patterns in children with EB. Healthcare professionals should be aware of joint hypermobility and its effect on gait in this patient cohort.

Linear correlation coefficients were calculated between the reported Young’s modulus (YM) values and non-covalent interactions within cellulose-oligolignol complexes, considering the composition of an efficient adhesive formulation previously reported. A paradigmatic relationship was observed. Molecular complexes of oligolignols with cellulose Iβ were modeled using hybrid quantum mechanics/molecular mechanics (QM/MM) computations to obtain wavefunctions at the interaction region. Subsequently, a study of non-covalent interactions (NCI) based on the atoms in molecules (AIM) theory was implemented, utilizing graphics processing units (GPUs) for calculations. Our findings indicate that non-covalent interactions control the forces associated to adhesive-cellulose contacts, primarily through X-H···O hydrogen bonds, which promote the adhesion of oligolignols on cellulose Iβ. Results indicate that the adhesion strength projected from larger YM values cannot be described solely by the number of stronger hydrogen bonds nor by the number of the weak interactions but by the entire contributions of specific interactions. Thus, significant linear correlations were observed between reported values of Young’s modulus and the molecular interactions observed, rendering the influence of oligolignol structure on the adhesion phenomenon in our cellulose Iβ crystallite model. These observations promote the NCI and AIM analysis in a new framework to design adhesive formulations.

The presence of defects in additive manufactured maraging steel is a widespread problem as its dependence on processing parameters significantly influences it. Using X-ray computed tomography, along with optical microscope data limited to 2D images, quantifies the internal porosity present on a compact tension sample typically employed in fatigue testing. The primary goal of this research is to analyse the pores obtained after the fabrication of a compact tension sample and their main definition parameters, such as sphericity, aspect ratio, surface, and volume, and obtain validation of which method is valid for each of the parameters analysed. The current study aims to enhance the understanding of defects in maraging steel samples through non-destructive 3D analysis. Conventional 2D analyses are limited to surface measurements, providing incomplete information. The proposed method will provide a comprehensive understanding of the defects inside the maraging steel sample, thereby improving the reliability of this material for further applications. This study will contribute to academic and industrial communities by providing a novel approach to analysing maraging steel samples and, ultimately, developing improved materials for various applications. The study’s findings reveal that most pores are produced by gases that are trapped in the fabrication process, and keyhole pores only appear near the surface.

Inductive thermography is an inspection technique that consists of the heating of a sample or a component by short induced eddy current pulses (duration of 50-100 ms) while an infrared camera records the evolution of the surface temperature. Surface cracks in metals can be excellently detected by this inspection technique. Both the eddy currents and the heat diffusion are disturbed by cracks, therefore becoming visible in the infrared images. The recorded image sequence is processed using the Fourier transform, and the resulting phase image is analysed directly by technicians (human-based detection) or developed defect detection algorithms (computer-based), to localize the defects. For industrial applications, the reliability of an inspection technique is very important. This is why it is necessary to calculate the probability of detection (POD) of the technology considered for each case study. The goal of this investigation is to compare the two standard parametric POD calculation techniques, ‘hit/miss’ and ‘â versus a’, for detecting surface cracks with inductive thermography on the nickel-based austenitic superalloy Inconel 718. First, artificial defects are considered for an ‘â vs a’ POD analysis and results are compared to finite element simulations. Additionally, real cracks on TIG welds, created with a Varestraint test machine, have also been considered and corresponding ‘hit/miss’ POD calculations have been performed. However, it is important to note, that the deeper a crack, the larger obstacle it creates for the eddy current and for the heat flow. Hence not only the defect length, but also its depth affects the signal around it. This implies that the calculated POD depends on both the crack length and depth and that in some cases ‘hit/miss’ POD analysis will not be enough.

The cohesin complex plays essential roles in chromosome segregation, 3D genome organisation, and DNA damage repair through its ability to modify DNA topology. In higher eukaryotes, meiotic chromosome function, and therefore fertility, requires cohesin complexes containing meiosis-specific kleisin subunits: REC8 and RAD21L in mammals and REC-8 and COH-3/4 in Caenorhabditis elegans. How these complexes perform the multiple functions of cohesin during meiosis and whether this involves different modes of DNA binding or dynamic association with chromosomes is poorly understood. Combining time-resolved methods of protein removal with live imaging and exploiting the temporospatial organisation of the C. elegans germline, we show that REC-8 complexes provide sister chromatid cohesion (SCC) and DNA repair, while COH-3/4 complexes control higher-order chromosome structure. High-abundance COH-3/4 complexes associate dynamically with individual chromatids in a manner dependent on cohesin loading (SCC-2) and removal (WAPL-1) factors. In contrast, low-abundance REC-8 complexes associate stably with chromosomes, tethering sister chromatids from S-phase until the meiotic divisions. Our results reveal that kleisin identity determines the function of meiotic cohesin by controlling the mode and regulation of cohesin–DNA association, and are consistent with a model in which SCC and DNA looping are performed by variant cohesin complexes that coexist on chromosomes.

In autonomous navigation and route planning, the data obtained by the different sensors play a significant role. On the one hand, more data will lead to faster learning of the behavioral policy. On the other hand, agents equipped with different sensors will need more computing power to process the data, thus requiring more robust equipment and increasing the cost of implementation. In addition, the complexity of the algorithms increases as different types of data, i.e., data with different structures, have to be synchronized. Therefore, this paper addresses the problem of homogenization and synchronization of data provided by heterogeneous sensors. Furthermore, it presents a novel method of estimating data in order to provide the agent with a 360-degree view of the environment, similar to that provided by a laser. The method’s performance compares the different behavioral policies obtained by different viewing angles of a camera with the policy obtained by a laser. The data obtained from the different viewing angles of each sensor are used in a path planning algorithm, which was designed to use a single 24-scan laser as an input source. The results show that the proposed method is robust since the behavior policies can be reused regardless of the viewing angle with which the sensor (camera) is provided. Furthermore, the proposed novel algorithm achieves an average efficiency of 68% and 94% using a 90 and 360-degree camera, respectively.

Abstract Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a receptor for the Wnt5a ligand that was shown to play a dual role in cancer. ROR2 was shown to either suppress or promote tumor progression in different tumor types by regulating the same biological processes (i.e. proliferation, invasion) in opposite ways. We have recently observed that ROR2 plays multiple and somewhat contradictory roles in melanoma where it impairs cell proliferation but promotes migration, EMT and chemoresistance. In the present article, ROR2 is proposed to be a major driver of “phenotype switching” in melanoma that can tilt the cellular behavior toward proliferative or invasive phenotypes. This function of ROR2 has therapeutic implications since it would provide an opportunity for targeting specific phenotypes such as invasive and drug-resistant ones by inhibiting ROR2.

This research focuses on analysing the 18Ni300 maraging steel produced through laser powder bed fusion. Specifically, it aims to examine the phase components using X-ray diffraction, the microstructure through scanning electron microscopy, and the hardness of the different structures present in the manufactured material. The primary goal is to meticulously analyse the material and its microstructures. By doing so, a correlation between the hardness and each structure type, be it cellular or columnar, can be established. This will allow us to pinpoint any defects in the material before any surface chemical treatment is carried out and facilitate a thorough examination of its microstructure. A consistent pattern emerges across the samples through systematic measurement of microhardness distribution in various locations and detailed examination of the structure. The findings of the study reveal that the hardness of cellular and columnar structures exhibits a significant variation based on the location of the measurement about cell boundaries. The hardness value is notably higher in the combination of cellular and multiple layers, as the data indicate.

In order to improve understanding of the fatigue behaviour in additive manufactured samples, this research delves into the challenging interplay between building parameters, particularly fabrication angles, and the presence of pores. The primary objective is to explore the characterisation of these pores and unravel their relationship with the fatigue properties of the material under investigation. Through a systematic analysis of porosity distribution in various fabrication orientations, supplemented by a detailed examination of the elemental dispersion around specific porous structures using energy-dispersive X-ray spectroscopy, a consistent behavioural pattern emerges across the samples. In assessing fatigue behaviour, an examination of the variables reveals that only area and aspect ratio significantly influence the behaviour of the samples. Such studies can contribute substantially to academic research in the field of material science and engineering.

This paper presents an extensive literature review focusing on the utilisation of crack tip plasticity as a crucial parameter in determining and enhancing crack growth models. The review encompasses a comprehensive analysis of various methodologies, predominantly emphasising numerical simulations of crack growth models while also considering analytical approaches. Although experimental investigations are not the focus of this review, their relevance and interplay with numerical and analytical methods are acknowledged. The paper critically examines these methodologies, providing insights into their advantages and limitations. Ultimately, this review aims to offer a holistic understanding of the role of crack tip plasticity in the development of effective crack growth models, highlighting the synergies and gaps between theoretical, experimental, and simulation-based approaches.

The CMT-Twin-based wire and arc additive manufacturing (WAAM) process for 5356 aluminium alloy has been investigated focusing on the optimisation of welding parameters to maximise the deposition rate while avoiding segregation-related problems during solidification. For that, different conditions have been studied regarding interpass dwell time and the use of forced cooling. The larger heat input produced by the double-wire CMT-Twin process, compared to the single-wire CMT, creates vast segregations for less intensive cooling conditions and short dwell times that can induce cracks and reduce ductility. Thermography has been applied to set a maximum local temperature between consecutive layers avoiding those segregations and pores, and to optimise the total manufacturing time by varying the interpass dwell time along the height of the wall. Only a constant interpass long dwell time of 240 s and the new optimised strategy were effective in avoiding merged segregations, reducing the latest total manufacturing time by 36%. Obtained tensile properties are comparable to other works using WAAM for this alloy, showing lower properties in the vertical orientation. The use of CMT-Twin-based welding technology together with variable interpass dwell time controlled by thermography is an interesting alternative to build up parts with wall thicknesses around of 10 mm in a reduced time.

Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatment timing or antibody serostatus. The Acute Optic Neuritis Network (ACON) presents a global, prospective, observational study protocol primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. Patients presenting within 30 days of the inaugural ON will be enrolled. For the primary analysis, patients will subsequently be assigned into the MS-ON group, the aquapotin-4-IgG positive ON (AQP4-IgG+ON) group or the MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from the onset of visual loss to high-dose corticosteroids (days-to-Rx). The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. In addition, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON, and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include low-contrast best-corrected visual acuity (LC-BCVA), optical coherence tomography (OCT), magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4-IgG and MOG-IgG levels, neurofilament, and glial fibrillary protein), and patient reported outcome measures (headache, visual function in daily routine, depression, and quality of life questionnaires) at presentation at 6-month and 12-month follow-up visits. Data will be collected from 28 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, and Australia. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON, and 50 MOG-IgG+ON. This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and the accuracy of diagnostic stratification in acute demyelinating ON.Trial registrationClinicalTrials.gov, identifier: NCT05605951.

Abstract Background ROR2 is a tyrosine-kinase receptor whose expression is dysregulated in many human diseases. In cancer, ROR2 stimulates proliferation, survival, migration, and metastasis, and is associated with more aggressive tumor stages. The purpose of this work is to study the role of ROR2 in the chemoresistance of melanoma. Methods Gain- and loss-of-function experiments were used to study the biological function of ROR2 in melanoma. Cell death induced by chemotherapeutic drugs and BH-3 mimetics was evaluated using crystal violet cytotoxicity assays and annexin V/propidium iodide staining. Western blots were used to evaluate the expression of proteins implicated in cell death. The differences observed between cells with manipulation of ROR2 levels and control cells were evaluated using both Student’s t-test and ANOVA. Results We describe that ROR2 contributes to tumor progression by enhancing the resistance of melanoma cells to both chemotherapeutic drugs and BH-3 mimetics. We demonstrate that ROR2 reduced cell death upon treatment with cisplatin, dacarbazine, lomustine, camptothecin, paclitaxel, ABT-737, TW-37, and venetoclax. This effect was mediated by the inhibition of apoptosis. In addition, we investigated the molecular mechanisms implicated in this role of ROR2. We identified the MDM2/p53 pathway as a novel target of ROR2 since ROR2 positively regulates MDM2 levels, thus leading to p53 downregulation. We also showed that ROR2 also upregulates Mcl-1 and Bcl2-xL while it negatively regulates Bax and Bid expression. The effect of ROR2 on the expression of these proteins is mediated by the hyperactivation of ERK. Conclusions These results demonstrate that ROR2 contributes to melanoma progression by inhibiting apoptosis and increasing chemoresistance. These results not only position ROR2 as a marker of chemoresistance but also support its use as a novel therapeutic target in cancer.

Aim: B-cell lymphoma-2 (Bcl-2)-like protein-10 (Bcl2L10) is the less studied member of Bcl-2 family proteins, with the controversial role in different cancer histotypes. Very recently, Bcl2L10 expression in melanoma tumor specimens and its role in melanoma response to therapy have been demonstrated. Here, the involvement of Bcl2L10 on the in vitro and in vivo properties associated with melanoma aggressive features has been investigated. Methods: Endogenous Bcl2L10 protein expression was detected by western blotting analysis in a panel of patient-derived and commercially available human melanoma cells. In vitro assays to evaluate clonogenicity, cell proliferation, cell migration, cell invasion, and in vitro capillary-like structure formation [vasculogenic mimicry (VM)] have been performed by using human melanoma cells stably overexpressing Bcl2L10 or transiently transfected for loss/gain function of Bcl2L10, grown under two- or three-dimensional (3D) conditions Xenograft melanoma model was employed to evaluate in vivo tumor growth and angiogenesis. Results: Results demonstrated that Bcl2L10 acts as an inducer of in vitro cell migration, invasion, and VM, while in vitro cell proliferation, in vivo tumor growth, as well as colony formation properties were not affected. Dissecting different signaling pathways, it was found that Bcl2L10 positively affects the phosphorylation of extracellular-signal-regulated kinase (ERK) and the expression of markers of cell invasion, such as urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs). Of note, Bcl2L10-dependent in vitro migration, invasion, and VM are linked to uPAR. Bcl2L10 also negatively regulates the intracellular calcium level. Finally, reduced invasion capability in 3D spheroid invasion assay of melanoma cells transiently overexpressing Bcl2L10 was observed after treatment with inhibitors of MMPs and uPAR. Conclusions: Overall, data reported in this paper provide evidence supporting a positive role of Bcl2L10 in melanoma aggressive features.

To know the overall regional or international scientific production is of vital importance to many areas of knowledge. Nevertheless, in interdisciplinary areas such as Geographic Information Science (GISc) it is not enough to just count papers published in specific journals. Most of them, as is the case of the International Journal of Remote Sensing (IJRS), welcome GISc papers but are not exclusive to that area so the production assignable to authors in the region must consider not only affiliation but also whether or not each paper falls into the theme of GISc. IJRS publishes far more papers than any other GISc journal, so it is important to assess quantitatively how many of them are of GISc. In this work, a representative sample of IJRS articles published over a period of almost 30 years was analyzed using a specific GISc definition. With these data, a manual classification methodology through a set of experts was carried out, and a dataset was built, analyzed, and statistically tested. As a result we estimate that between 47 and 76% of the IJRS articles can be considered from GISc, with a confidence level of 95%. Aside from the primary goal, this set could be used as a gold standard for future classification tasks. It constitutes the first GISc dataset of this kind, that may be used to train artificial intelligence systems capable of performing the same classification automatically and in a massive way. A similar procedure could be applied to other interdisciplinary fields of knowledge as well.

Abstract Background Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma. Methods Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma. Proliferation assays, flow cytometry, and western blotting were used to evaluate cell proliferation and changes in expression levels of cell-cycle and proliferation markers. The role of ROR2 in tumor growth was assessed in xenotransplantation experiments followed by immunohistochemistry analysis of the tumors. The role of ROR2 in melanoma patients was assessed by analysis of clinical data from the Leeds Melanoma Cohort. Results Unlike previous findings describing ROR2 as an oncogene in melanoma, we describe that ROR2 prevents tumor growth by inhibiting cell-cycle progression and the proliferation of melanoma cells. The effect of ROR2 is mediated by inhibition of Akt phosphorylation and activity which, in turn, regulates the expression, phosphorylation, and localization of major cell-cycle regulators including cyclins (A, B, D, and E), CDK1, CDK4, RB, p21, and p27. Xenotransplantation experiments demonstrated that ROR2 also reduces proliferation in vivo, resulting in inhibition of tumor growth. In agreement with these findings, a higher ROR2 level favors thin and non-ulcerated primary melanomas with reduced mitotic rate and better prognosis. Conclusion We conclude that the expression of ROR2 slows down the growth of primary tumors and contributes to prolonging melanoma survival. Our results demonstrate that ROR2 has a far more complex role than originally described.

Bubble drag reduction has been shown to be a promising technique for reducing the drag in ships, thus reducing the emission of pollutants and allowing the compliance with the new requirements imposed recently in this respect. Different searches have been conducted in the publications related to this technique, and an increase in interest has been shown, especially in the last decade. In this context, a review of the experimental work related to bubble drag reduction published in the last decade is presented in the present article. The works were classified according to the facility used (towing tank, cavitation tunnel, water channel, Taylor–Couette…), and the main finding are presented. It was found that two new trends in research have arisen, while there are still contradictions in the fundamental basis, which needs further study.

This work presents a new approach for studying crack growth resulting from fatigue, which utilizes the plastic contribution of crack-tip opening displacement (CTODp). CTODp is used to predict austenitic stainless-steel crack propagation. Unlike linear elastic fracture mechanics analysis, the method presented here is also helpful for tasks other than small-scale yielding. The approach was based on correlating full-field displacement information with post-processing digital images. This work describes a detailed post-processing protocol that can be used to calculate CTODp. The results for steel compact-tension specimens were especially promising. Of note, there was a linear relationship between the propagation rate of fatigue cracks and the CTODp range.

In this work, the influence of the tool geometry on friction stir spot welding (FSSW) was studied on sheets made of AA6061-T6 aluminum alloy. Four different AISI H13 tools with simple cylindrical and conical pin profiles and 12 mm and 16 mm shoulder diameters were used to perform the FSSW joints. Sheets of 1.8 mm thickness were used during the experimental work to prepare the lap-shear specimens. The FSSW joints were performed at room temperature. For each joining condition, four specimens were carried out. Three specimens were used to find the value of the average tensile shear failure load (TSFL), while the fourth one was used to examine the micro-Vickers hardness profile and to observe the microstructure of the cross-section of the FSSW joints. The investigation concluded that higher mechanical properties corresponding to the finer microstructure were obtained by the conical pin profile and the higher shoulder diameter compared with the specimens performed using the cylindrical pin tool and lower shoulder diameter due to the higher strain hardening and the higher frictional heat generation, respectively.

Background An early and prolonged lockdown was adopted in Argentina during the first wave of COVID-19. Early reports evidenced elevated psychological symptoms. Aims To explore if the prolonged lockdown was associated with elevated anxiety and depressive symptoms; if mental fatigue was associated with lockdown adherence (a phenomenon called ‘behavioural fatigue’); and if financial concerns were associated with lockdown adherence and emotional symptoms. Method The survey included standardised questionnaires to assess depressive (PHQ-9) and anxious (GAD-7) symptoms, mental fatigue, risk perception, lockdown adherence, financial concerns, daily stress, loneliness, intolerance to uncertainty, negative repetitive thinking and cognitive problems. LASSO regression analyses were carried out to predict depression, anxiety and lockdown adherence Results The survey reached 3617 adults (85.2% female) from all provinces of Argentina after 72 days of lockdown. Data were collected between 21 May 2020 and 4 June 2020. In that period, Argentina had an Oxford stringency index of 85/100. Of those surveyed, 45.6% and 27% met the cut-offs for depression and anxiety, respectively. Mental fatigue, cognitive failures and financial concerns were correlated with psychological symptoms, but not with adherence to lockdown. In regression models, mental fatigue, cognitive failures and loneliness were the most important variables to predict depression, intolerance to uncertainty and lockdown difficulty were the most important for anxiety, and perceived threat was the most important for predicting lockdown adherence. Conclusions During the extended lockdown, psychological symptoms increased, being enhanced by mental fatigue, cognitive difficulties and financial concerns. We found no evidence of behavioural fatigue. Thus, feeling mentally fatigued is not the same as being behaviourally fatigued.

Although the infralimbic cortex (IL) is not thought to play a role in fear acquisition, recent experiments found evidence that synaptic plasticity is occurring at ventral hippocampal (vHPC) synapses in IL during auditory fear acquisition as measured by changes in the N-methyl-D-aspartate (NMDA) receptor-mediated currents in male rats. These electrophysiological data suggest that fear conditioning changes the expression of NMDA receptors on vHPC-to-IL synapses. To further evaluate the plasticity of NMDA receptors at this specific synapse, we injected AAV particles expressing channelrhodopsin-EYFP into the vHPC of male and female rats to label vHPC projections with EYFP. To test for NMDA receptor changes in vHPC-to-IL synapses after fear learning, we used fluorescence-activated cell sorting (FACS) to quantify synaptosomes isolated from IL tissue punches that were positive for EYFP and the obligatory GluN1 subunit. More EYFP+/GluN1+ synaptosomes with greater average expression of GluN1 were isolated from male rats exposed to auditory fear conditioning (AFC) than those exposed to context and tones only or to contextual fear conditioning (CFC), suggesting that AFC increased NMDA receptor expression in males. In a second experiment, we found that pairing the tones and shocks was required to induce the molecular changes and that fear extinction did not reverse the changes. In contrast, females showed similar levels of EYFP+/GluN1+ synaptosomes in all behavioral groups. These findings suggest that AFC induces synaptic plasticity of NMDA receptors in the vHPC-to-IL projection in males, while female rats rely on different synaptic mechanisms.

Normal function of the placenta depends on the earliest developmental stages when trophoblast cells differentiate and invade into the endometrium to establish the definitive maternal-fetal interface. Previously, we identified the ubiquitously expressed tumour suppressor BRCA1-associated protein 1 (BAP1) as a central factor of a novel molecular node controlling early mouse placentation. However, functional insights into how BAP1 regulates trophoblast biology are still missing. Using CRISPR/Cas9 knockout and overexpression technology in mouse trophoblast stem cells, here we demonstrate that the downregulation of BAP1 protein is essential to trigger epithelial-mesenchymal transition (EMT) during trophoblast differentiation associated with a gain of invasiveness. Moreover, we show that the function of BAP1 in suppressing EMT progression is dependent on the binding of BAP1 to additional sex comb-like (ASXL1/2) proteins to form the polycomb repressive deubiquitinase (PR-DUB) complex. Finally, both endogenous expression patterns and BAP1 overexpression experiments in human trophoblast stem cells suggest that the molecular function of BAP1 in regulating trophoblast differentiation and EMT progression is conserved in mice and humans. Our results reveal that the physiological modulation of BAP1 determines the invasive properties of the trophoblast, delineating a new role of the BAP1 PR-DUB complex in regulating early placentation.

Queued Radio Frequency Identification (RFID) networks arise naturally in many applications, where tags are grouped into batches, and each batch must be processed before the next reading job starts. In these cases, the system must be able to handle all incoming jobs, keeping the queue backlogs bounded. This property is called stability. Besides, in RFID networks, it is common that some readers cannot operate at the same time, due to mutual interferences. This fact reduces the maximum traffic that readers can process since they have to share the channel. Synchronous networks share the channel using a TDMA approach. The goal of this work is to analytically determine whether a synchronous queued RFID network attains stable operation under a given incoming traffic. Stability depends on the service rate, which is characterized in this paper using an exact numerical method based on a recursive analytical approach, overcoming the limitations of previous works, which were based on simplifications. We also address different flow optimization problems, such as computing the maximum joint traffic that a network can process stably, selecting the minimal number of readers to process a given total load, or determining the optimal timeslot duration, which are novel in the RFID literature.

Abstract Background The PI3K/Akt and the STAT3 pathways are functionally associated in many tumor types. Both in vitro and in vivo studies have revealed that either biochemical or genetic manipulation of the STAT3 pathway activity induce changes in the same direction in Akt activity. However, the implicated mechanism has been poorly characterized. Our goal was to characterize the precise mechanism linking STAT3 with the activity of Akt and other AGC kinases in cancer using melanoma cells as a model. Results We show that active STAT3 is constitutively bound to the PDK1 promoter and positively regulate PDK1 transcription through two STAT3 responsive elements. Transduction of WM9 and UACC903 melanoma cells with STAT3-small hairpin RNA decreased both PDK1 mRNA and protein levels. STAT3 knockdown also induced a decrease of the phosphorylation of AGC kinases Akt, PKC, and SGK. The inhibitory effect of STAT3 silencing on Akt phosphorylation was restored by HA-PDK1. Along this line, HA-PDK1 expression significantly blocked the cell death induced by dacarbazine plus STAT3 knockdown. This effect might be mediated by Bcl2 proteins since HA-PDK1 rescued Bcl2, Bcl-XL, and Mcl1 levels that were down-regulated upon STAT3 silencing. Conclusions We show that PDK1 is a transcriptional target of STAT3, linking STAT3 pathway with AGC kinases activity in melanoma. These data provide further rationale for the ongoing effort to therapeutically target STAT3 and PDK1 in melanoma and, possibly, other malignancies.

The current state of the art in compliant actuation has already good performance, but this is still insufficient to provide a decent autonomy for the next generation of robots. In this paper, a next step is taken to improve the efficiency of actuators by tackling and enhancing the Series-Parallel Elastic Constant Torque Actuation (SPECTA) concept, which has previously been analyzed in simulations. In this work, the efficiency is increased further by decoupling the springs and their driving parts through the use of locking mechanisms, such that the motors are not always loaded and the springs can easily store energy from both input or output. Simulations have been performed to confirm this and they also showed that, in the SPECTA concept, it is always better to use high-speed motors instead of high-torque motors, even with non-efficient gearing. In this paper, the SPECTA concept is also validated experimentally with the use of a newly built test setup. In light of the obtained results, showing an increase in efficiency for almost all working points, it can be stated that SPECTA is a promising new actuation technology that allows for an increase in energy recuperation, efficiency, and autonomy.

The fatigue overload behaviours of coarse grain (~30 μm), ultrafine grain (360 nm) and nanocrystalline (~30 nm) Ni are compared under constant amplitude loading at R = 0.1 after a 100% overload. Synchrotron X-ray diffraction is applied to map the elastic crack-tip strain fields at the mid-thickness of a compact tension specimen of nanocrystalline Ni at various stages through the loading cycles, from which the variation in stress before, during and after overload is estimated. Digital image correlation is used to measure the crack length and the displacement fields at the specimen surfaces for both grain sizes, from which the fatigue crack growth (FCG) rate, crack opening displacement and stress intensity factor range are determined. The FCG for coarse grain Ni is most significantly retarded whereas the nanocrystalline Ni is least affected by the overload due to an increased yield stress and a more planar crack surface morphology. As a result, FCG retardation by plasticity, surface roughness and residual stress-induced crack closure are reduced. Keywords: Nanocrystalline, Retardation mechanisms, Energy dispersive X-ray diffraction, Crack path, J-integral

Abstract Background Triatoma infestans (Hemiptera: Reduviidae) is the main vector of Trypanosoma cruzi, the etiological agent of Chagas disease, in South America. Active dispersal of this vector is the principal cause of recolonization of human dwellings previously treated with insecticides. Due to the persistence of vector populations and their movement between habitats, dispersive behavior studies are important for understanding the epidemiology of Chagas disease. The aim of this study was to analyze the relationship among T. infestans females’ activity levels according to their physiological conditions. Results Two groups of insects were used, unfed and fed females. Each was composed of three subgroups in relation to the reproductive state: fifth-stage nymphs, virgin and fertilized females. There was a significant interaction between reproductive and nutritional states among T. infestans female’ activity levels. During the experiments, unfed and fed nymphs remained inactive. Virgin females showed a dual behavior in their movement; fasted insects were more active. Fertilized females, both fed and unfed, were always active. Conclusion The reproductive and nutritional conditions of T. infestans females affect their activity levels. When females with different reproductive states remained together, fertilized females showed permanent activity levels, suggesting that this subgroup of females represents the highest epidemiological risk as colonizers of human dwellings.

Accurate knowledge of the plastic zone of fatigue cracks is a very direct and effective way to quantify the damage of components subjected to cyclic loads. In this work, we propose an ultra-fine experimental characterisation of the plastic zone based on Vickers micro-indentations. The methodology is applied to different compact tension (CT) specimens made of aluminium alloy 2024-T351 subjected to increasing stress intensity factors. The experimental work and sensitivity analysis showed that polishing the surface to #3 μm surface finish and applying a 25 g-force load for 15 s produced the best results in terms of resolution and quality of the data. The methodology allowed the size and shape of both the cyclic and the monotonic plastic zones to be visualised through 2D contour maps. Comparison with Westergaard’s analytical model indicates that the methodology, in general, overestimates the plastic zone. Comparison with S355 low carbon steel suggests that the methodology works best for alloys exhibiting a high strain hardening ratio.

N. Meningitidis serogroup (A, B, C), are main causers of disease. Serogroup W-135 incidence is lower nowadays and, although it is increasing, is such an uncommon infection in adults. We report a case of a monoarthritis knee due to Neisseria meningitidis ( W- 135 ) in an inmunocompetent 50 year- old male.

La interrupción de las trayectorias educativas de los adolescentes uruguayos es un tema de preocupación nacional por los efectos negativos que tiene en sus trayectorias vitales. La literatura nacional e internacional muestra que estas interrupciones son más frecuentes en varones que en mujeres, la utilización de la perspectiva de género contribuye a explicar esta brecha. Este artículo presenta los resultados de una investigación cuyo objetivo fue indagar la relación entre la construcción subjetiva de masculinidad y las trayectorias y percepciones educativas de adolescentes varones residentes de Montevideo. Se trató de un estudio cualitativo, con una muestra teórica cuyo criterio de selección combinó características de homogeneidad (varones, de 15 a 17 años, residentes de Montevideo, que hubiesen interrumpido su trayectoria escolar al menos hace un año) con criterios de heterogeneidad (zonas con mejores indicadores educativos y nivel socioeconómico y zonas con características opuestas). Se hicieron 29 entrevistas semiestructuradas, del análisis de estas se concluye que los varones se auto perciben con menores posibilidades para completar su trayectoria educativa debido a características propias de su género, especialmente en tres áreas: el vínculo familiar, su visión y vínculo con el sistema educativo y la relación de los varones con el consumo de sustancia.

A study on the accuracy of the approximation of the displacement field around of crack tip in a sample made from bridge steel (S355) is main objective of contribution. Linear elastic fracture mechanics (LEFM) theory in framework of multi-parameter formulation, i.e. postulated by Williams is used to determine of coefficients of Williams power series terms. Over deterministic method was used to calculate the terms based on the least squares regression technique, applied on data from numerical simulation and experiment on S355 steel grades. Comparison between the stress fields (by principal stress s1 and von Mises stress sHMH) obtain from experimental measurement DIC, Hybrid method and obtain from reconstruction by using various number of Williams power terms are quantified in order to get key information around the crack tip region on bridge steel specimens.

The transfer of charge at the molecular level plays a fundamental role in many areas of chemistry, physics, biology and materials science. Today, more than 60 years after the seminal work of R. A. Marcus, charge transfer is still a very active field of research. An important recent impetus comes from the ability to resolve ever faster temporal events, down to the attosecond time scale. Such a high temporal resolution now offers the possibility to unravel the most elementary quantum dynamics of both electrons and nuclei that participate in the complex process of charge transfer. This review covers recent research that addresses the following questions. Can we reconstruct the migration of charge across a molecule on the atomic length and electronic time scales? Can we use strong laser fields to control charge migration? Can we temporally resolve and understand intramolecular charge transfer in dissociative ionization of small molecules, in transition-metal complexes and in conjugated polymers? Can we tailor molecular systems towards specific charge-transfer processes? What are the time scales of the elementary steps of charge transfer in liquids and nanoparticles? Important new insights into each of these topics, obtained from state-of-the-art ultrafast spectroscopy and/or theoretical methods, are summarized in this review.

The main goal of this work is describing the experience in using Project Based Learning (PBL) methodology in Materials Science courses in several Engineering degrees. The courses were taught simultaneously in four different Spanish universities. In addition, the impact of this proposal on the acquisition of transversal skills through the perceptions of students and teachers is assessed. In order to do so, voices of over 54 students and 5 lecturers involved in the work have been gathered and studied descriptively. Discussion groups and self-reports have been collected and subsequently analysed. The analysis of the data collected by these two instruments has been coded and categorized into general dimensions. The results show how, through the PBL, self-learning is encouraged and the development of transversal skills such as teamwork are enhanced. Meanwhile, the lecturers consider PBL an appropriate methodology for Materials Science courses; however its implementation requires a higher work load. The faculty acknowledged PBL as a very interesting tool to work and evaluate transversal competences. Hence, the PBL methodology stands as one of the most effective methods that meet the demands of the 21st century and enables students to acquire not only content based knowledge, but also other abilities.

Wnt5a signaling has been implicated in the progression of cancer by regulating multiple cellular processes, largely migration and invasion, epithelial-mesenchymal transition (EMT), and metastasis. Since Wnt5a signaling has also been involved in inflammatory processes in infectious and inflammatory diseases, we addressed the role of Wnt5a in regulating NF-κB, a pivotal mediator of inflammatory responses, in the context of cancer. The treatment of melanoma cells with Wnt5a induced phosphorylation of the NF-κB subunit p65 as well as IKK phosphorylation and IκB degradation. By using cDNA overexpression, RNA interference, and dominant negative mutants we determined that ROR1, Dvl2, and Akt (from the Wnt5a pathway) and TRAF2 and RIP (from the NF-κB pathway) are required for the Wnt5a/NF-κB crosstalk. Wnt5a also induced p65 nuclear translocation and increased NF-κB activity as evidenced by reporter assays and a NF-κB-specific upregulation of RelB, Bcl-2, and Cyclin D1. Further, stimulation of melanoma cells with Wnt5a increased the secretion of cytokines and chemokines, including IL-6, IL-8, IL-11, and IL-6 soluble receptor, MCP-1, and TNF soluble receptor I. The inhibition of endogenous Wnt5a demonstrated that an autocrine Wnt5a loop is a major regulator of the NF-κB pathway in melanoma. Taken together, these results indicate that Wnt5a activates the NF-κB pathway and has an immunomodulatory effect on melanoma through the secretion of cytokines and chemokines.

In this work, the multiaxial fatigue behaviour of 316 and 304 stainless steel was studied. The study was based on the critical plane approach which is based on observations that cracks tend to nucleate and grow in specific planes. Three different critical plane models were employed to this end, namely Fatemi−Socie (FS), Smith−Watson−Topper (SWT) and the newly proposed Sandip−Kallmeyer−Smith (SKS) model. The study allowed equi-biaxial stress state, mean strain and non−proportional hardening effects to be taken into consideration. Experimental tests including different combinations of tension, torsion and inner pressure were performed and were useful to identify the predominant failure mode for the two materials. The results also showed that the SKS damage parameter returned more conservative results than FS with lower scatter level in both materials, with prediction values between FS and SWT.

The effect of the incorporation of Er2O3-doped particles on the structural and luminescence properties of phosphate glasses was investigated. A series of different Er2O3-doped TiO2, ZnO, and ZrO2 microparticles was synthesized using soft chemistry and then added into various phosphate glasses after the melting at a lower temperature than the melting temperature. The compositional, morphological, and structural analyses of the particles-containing glasses were performed using elemental mapping by field emission-scanning electron microscopy (FE-SEM) with energy dispersive x-ray spectrometry (EDS) and x-ray diffraction (XRD). Additionally, the luminescence spectra and the lifetime values were measured to study the influence of the particles incorporation on the spectroscopic properties of the glasses. From the spectroscopic properties of the glasses with the composition 50P2O5-40SrO-10Na2O, a large amount of the Er2O3-doped particles is thought to dissolve during the glass melting. Conversely, the particles were found to survive in glasses with a composition 90NaPO3-(10 − x)Na2O-xNaF (with x = 0 and 10 mol %) due to their lower processing temperature, thus clearly showing that the direct doping method is a promising technique for the development of new active glasses.

This work analyses the prediction capabilities of a recently developed critical plane model, called the SKS method. The study uses multiaxial fatigue data for S355-J2G3 steel, with in-phase and 90° out-of-phase sinusoidal axial-torsional straining in both the low cycle fatigue and high cycle fatigue ranges. The SKS damage parameter includes the effect of hardening, mean shear stress and the interaction between shear and normal stress on the critical plane. The collapse and the prediction capabilities of the SKS critical plane damage parameter are compared to well-established critical plane models, namely Wang-Brown, Fatemi-Socie, Liu I and Liu II models. The differences between models are discussed in detail from the basis of the methodology and the life results. The collapse capacity of the SKS damage parameter presents the best results. The SKS model produced the second-best results for the different types of multiaxial loads studied.

Understanding the earth as a system requires integrating many forms of data from multiple fields. Builders and funders of the cyberinfrastructure designed to enable open data sharing in the geosciences risk a key failure mode: What if geoscientists do not use the cyberinfrastructure to share, discover and reuse data? In this study, we report a baseline assessment of engagement with the NSF EarthCube initiative, an open cyberinfrastructure effort for the geosciences. We find scientists perceive the need for cross-disciplinary engagement and engage where there is organizational or institutional support. However, we also find a possibly imbalanced involvement between cyber and geoscience communities at the outset, with the former showing more interest than the latter. This analysis highlights the importance of examining fields and disciplines as stakeholders to investments in the cyberinfrastructure supporting science.